This application requests funds for a triple quadrupole mass spectrometer with unique capabilities for quantitating specific proteins and other biological molecules using an approach known as multiple reaction monitoring (MRM). A group of very experienced investigators, with access currently to a number of high resolution and tandem mass spectrometers for identifying and characterizing protein structures, will use this instrument and the MRM technique for targeted analyses requiring considerably higher sensitivity and quantitative measurements from large numbers of samples. Four laboratories will constitute the major users: the Middle Atlantic Mass Spectrometry (MAMS) Laboratory directed by Robert J. Cotter, the Johns Hopkins SOM Mass Spectrometry Proteomics Facility directed by Robert Cole, and the research laboratories of Akhilesh Pandey and Gerald Hart. Major projects also include a number of investigators collaborating directly with the MAMS and MS/Proteomics laboratories. For a number of the projects proposed to utilize this instrument, MRM provides a more sensitive and selective approach than the iTRAQ measurements currently used by this group of investigators in studies on genetics, Down syndrome, HIV and dementia, diabetes and cancers of the lung, pancreas and liver. Additionally, the constant neutral loss (CNL) and precursor ion scan modes of this instrument will be used to screen for ubiquitylated and SUMOylated proteins and for nitrosylated protein biomarkers associated with oxidative stress. PUBLIC HEALTH RELEVANCE: This application requests funds for a mass spectrometer capable of screening for specific proteins and other biological molecules with high sensitivity from large numbers of samples. The results from, for example, a large patient cohort composed of disease and control individuals may be used to identify biomarkers for disease diagnosis, for monitoring the outcomes of therapies, or to establish the biochemical pathways needed to design new drugs. This group of investigators will utilize the instrument in studies on genetics, Down syndrome, HIV and dementia, diabetes and cancers of the lung, pancreas and liver.